To evaluate the feasibility of developing serodiagnostic tests for detecting Mycobacterium avium complex (MAC) infections, antibodies to MAC antigens were measured by ELISA and immunoblot assays in 20 patients with AIDS and disseminated MAC disease, 5 HIV-seronegative patients with pulmonary MAC infections, and 20 healthy controls. Wheras ELISA titers for healthy controls and patients with AIDS and MAC disease were comparable, HIV-seronegative patients with MAC disease had higher anti-MAC antibody titers (P<0.01). Immunoblot analyses with the same M. avium sonic extracts indicated that each of the three groups had a limited heterogeneous response to M. avium antigens. No significant differences in immunoblot reactivities were detected. However, immunoblot studies with recombinant nontuberculous mycobacterial antigens revealed that over 90% of the patients with MAC disease and only 25% of controls recognized a recombinant protein derived from a 35 kDa mycobacterial protein. Although sonic extracts do not permit adequate discrimination of antibody reactivity in patients with MAC disease, recombinant antigens may be useful indicators of disease. We have also been utilizing MAC-specific monoclonal antibodies to detect M. avium antigens in the sera of AIDS patients with MAC disease. We are currently testing a protocol that permits the detection of MAC antigen in AIDS patient sera using MAb 4004 F1, an antibody that reacts specifically with a 20 kDa MAC protein.